Transcranial direct current stimulation (tDCS) is one type of neuromodulation, which is an emerging technology that holds promise for the future studies on therapeutic and diagnostic applications in treatment of neurological and psychiatric diseases. Epilepsy is a major problem with devastating effects on patients and their caregivers and has a tremendous socioeconomic impact on families and health-care systems in the Saudi Arabia and worldwide. tDCS is a low-cost, noninvasive portable neuromodulation technique which can transiently decrease or increase cortical excitability in humans and which was invasively demonstrated to reduce epileptiform discharges in animals. This article reviews the tDCS as tools of neuromodulation for epilepsy and discusses the opportunities and challenges available for clinicians and researchers interested in advancing neuromodulation therapy. The aim of this review is to highlight the usefulness of tDCS and to generate an interest that will lead to appropriate studies that assess the true clinical value of tDCS for epilepsy among local clinician and scientist.

Epilepsy is considered as fourth most prominent neurological disorder in the world that can affect people of all age groups and has devastating effects on patients and their caregivers and has a tremendous socioeconomic impact on families and health-care systems.[1] An individual with epilepsy suffers recurrent seizures unprovoked by acute brain insults or metabolic disorders. Seizures are defined by a brief period of uncontrolled involuntary trembling. They may be focus, involving only one part of the body, or simplified, involving the entire body, and they may be supplemented by loss of consciousness and of control of bowel or bladder function. Some individuals continue to have frequent seizures despite optimal treatment with antiepileptic drugs. However, more than 70% of patients who are treated achieve long-term remission or freedom from seizures, normally within 5 years of diagnosis.[2] Economical epilepsy treatments are available and an accurate diagnosis can be made without technological equipment.

Furthermore, all antiepileptic medications have possibly significant adverse effects including impairment of cognitive function, depression, agitation, sedation, liver failure, respiratory depression, Stevens-Johnsons syndrome, and numerous others. As a result, even patients with epilepsy that is controlled by medications often suffer from debilitating side effects. Therefore, new therapeutic modalities are straightway desired. The field of epilepsy research has been turning steadily toward nonpharmacologic options such as focal brain stimulation.[3] Brain stimulation techniques are principally advantageous in so far as they can be directed toward the regional irregularities that are believed to be abnormal in patients with focal epilepsy, can be targeted toward specific locations, and lack systemic side effects. Recently, a surgically implanted device that utilizes electrical stimulation has recently been approved for the treatment of epilepsy patients.[4] However, this device requires invasive surgical identification of the seizure focus, and the placement of hardware in the skull and brain, and thus carries significant morbidity.

Noninvasive neurostimulation techniques include cathodal transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). Of these, tDCS is uniquely suited to mass distribution and treatment, even at home, as it is lightweight, portable, inexpensive, and has a favorable safety profile. Some small preliminary studies suggest that cathodal tDCS may suppress epileptic seizures.[5],[6],[7] However, a well-powered randomized controlled trial demonstrating convincing proof of efficacy has not been conducted.

Electroencephalogram (EEG) is an important test for diagnosing epilepsy because it records the electrical activity of the brain. It is safe and painless. Each EEG montage or trace corresponds to a different region of the brain. The abnormal waveforms include spikes, sharp waves, and spike-and-wave discharges. Spikes and sharp waves along with slow waves in a specific area of the brain, such as the left temporal lobe, indicate that focus seizures might possibly come from that area. Primary generalized epilepsy, on the other hand, is suggested by spike-and-wave discharges that are widely spread over both hemispheres of the brain, especially if they begin in both hemispheres at the same time.

Unfortunately, EEG, although is the principal diagnostic test for epilepsy diagnosis, is a passive measure of cortical activity, and epileptiform discharges are usually sporadic events. Consequently, the sensitivity of a single EEG is only 29%–55%,[8],[9],[10],[11],[12] and 8% of patients will never have interictal discharges.[13],[14]

This turns out to be especially challenging when bearing in mind epilepsy mimics such as psychogenic nonepileptic attacks, cardiogenic syncope, and recurrent dystonias/tremors. Psychogenic nonepileptic seizures are caused by a psychopathological process and consist of paroxysmal behavioral changes that resemble an epileptic seizure but are not associated with electrophysiological epileptic changes.

Photic stimulation is useful for activation of generalized epileptiform discharges and has not been used for partial seizures. Several studies have documented that sleep deprivation can increase the chance of detecting epileptiform discharges in both partial and generalized epilepsies.[15],[16],[17] This is mainly due to the effect of sleep deprivation and not the sleep per se. Activating procedures can increase the yield of detecting interictal epileptiform discharges. Hyperventilation is particularly useful for primary generalized epilepsies; however, it can also activate focal epileptiform discharges in up to 10% in partial epilepsies.[18],[19] Thus, EEG can neither rule in nor rule out the diagnosis. However, still EEG is one of the most important tools for diagnosis of epilepsy. It helps in easy monitoring as well as proper management of neurological disorders. However, the visual perception of this complicated waveform analysis is not without difference of opinions and demands highly skilled interpreters for disease detection and diagnosis.

Transcranial Direct Current Stimulation

A constant current stimulator and surface electrodes soaked in normal saline are required for tDCS. The former is the source of steady flow of 0–4 mA direct current (DC) and it continually monitors the resistance in the system. Saline-soaked electrodes based on the scalp over desired areas ([e.g., the left or right precentral gyrus region (corresponding to C3 or C4 of the International 10-20 EEG system)]) make terminal relaying currents across the scalp and through the underlying brain tissue. tDCS is a noninvasive brain stimulation technique that induces polarity-dependent (anodal electrode increase excitability and cathode decrease excitability) alterations of cortical excitability.

The mechanisms by which cathodal DC reduces neuronal firing likely relate to hyperpolarization of the soma membrane which occurs when the apical dendrites neuron are oriented toward the cathode in a constant electric field.[20],[21],[22] The practical application of tDCS is simple: low amplitude DC is administered through scalp electrodes such that the cerebral cortex is exposed to cathodal DC beneath one of the electrodes, and the return (anodal) electrodes can be placed anywhere else on the body or in more complex arrangements to minimize currents at any site. tDCS methods have also recently been adapted to rats for work with disease models.[23],[24] Hundreds of tDCS trials have demonstrated the technique to be well tolerated and safe. Direct electrical current stimulation is presently FDA approved for extracranial use, and Food and Drug Administration applications for cranial stimulation (tDCS) for the management of mood disorder and chronic pain are in progress.[24] tDCS units are also inexpensive and lightweight. The electrical supply can be derived from conventional 9-volt batteries. The scalp electrodes can be fastened in seconds. tDCS can be combined easily with other therapies such as those that may be required for resuscitation of an acutely injured patient. tDCS is presently under investigation as a treatment for epilepsy, where excess cortical excitability is a prominent feature of the disease process, and where neuronal inhibition may be beneficial. Thus, for epilepsy, tDCS may offer a practical nonpharmacologic therapy for the large minority, approximately 35%, of patients whose seizure cannot be controlled by medication.

It is established in animal models including research by our own international collaborator that cathodal DC stimulation can inhibit epileptiform activity, seizures, and reduce associated damage;[23] to our knowledge, because cathodal DC hyperpolarize cell soma which in turn suppress excitability, it has been effective in every epilepsy animal model tested. In thefirst randomized sham-controlled trial of tDCS in epilepsy,[5],[6],[7] a single 20 min session of tDCS applied with the cathode over regions of cortical malformations in patients with refractory epilepsy resulted in a significant reduction in the frequency of interictal discharges, and a trend toward decreased seizure frequency. A recent study in children with refractory epilepsy demonstrated similar results.[6]

To start using tDCS in Kingdom of Saudi Arabia, we have to plan for four main initiatives: trained human resources, social marketing, medico-ethical regulations, and financial investments (hardware and physical space). Planning for thefirst generation of experts as clinicians, technicians, and trainers should be one of the most importantfirst steps. Holding practical and hands-on workshops could be the best option to reach this goal. The most preferable setting to start tDCS in center or institute would be in a hospital or clinic affiliated with a university. By originating from a respected academic center, it is essential for all medical professionals to understand and appreciate the benefits and limitations of tDCS technology for it to gain acceptance as a viable option.

Although tDCS is still in its infancy, preliminary research is promising. This is an excellent time for Kingdom of Saudi Arabia, through regional and global partnerships, to take the lead in the development and refinement of this technology, by exploring different pathologies, sites of stimulation, and determining the best parameters of stimulation.

Policymakers, granting agencies, regulating bodies, researchers, clinicians, and even public audiences should be targeted with educational programs regarding potentials, threads, challenges, hopes, abuse potentials, and regulations for clinical use of tDCS.

In fact, because applications in these fields are currently in the research stage, fixed protocols and safety guidelines are yet to be defined.[25],[26] Intervening in the brain is always fraught with the potential for serious consequences. Despite these concerns, only by conducting carefully planned clinical and experimental studies can we provide the impetus to advance care for people with brain, emotional or psychological, or neuropsychiatric disorders.

Economic Effects of Epilepsy

Economically, epilepsy has a huge effect, with almost 5% of the medical costs of industrialized countries given to the disease. Although in real terms morbidity is relatively low, the long-term impairments left behind are hugely detrimental both in terms of hospital and other care sector costs

Technical Limitation of Transcranial Direct Current Stimulation in Experimental Settings

In comparison to TMS, the major limitation of tDCS is that it is not focal and “strong” enough to map cortical functions precisely. However, in comparison to TMS, tDCS requires inexpensive hardware and the procedure is simple. The most important component is a current generator, which is capable of delivering a constant electrical current flow of up to 2 mA. In principal, the building of such a battery-driven device should not be a complicated task for an experienced electronic engineer. Furthermore, it cannot produce temporally focused effects like TMS. On the other hand, applying tDCS is simple. Blinding of subjects and investigators is easier, thereby allowing the conduct of more robust double-blind and sham-controlled trials. Further studies, particularly in humans, are required to understand and verify tDCS actions on brain tissue, its mechanisms, and the associated behavioral and cognitive effects.

Conclusions

Epilepsy is a leading cause of death and neurological disability in adults, inflicting a heavy burden on affected individuals and their families. There is still high rate of mortality or dependence where access to new technologies and expert facilities is available, making it imperative that new treatments and technologies are discovered and exploited in the battle against epilepsy.